The short-term deleterious effects of acute kidney injury (AKI) on morbidity and mortality are well-known from several epidemiological studies. However, the long-term sequelae of AKI have not been thoroughly explored. Although AKI has been widely considered a reversible disease, studies now suggest that AKI may cause or contribute to progression of chronic kidney disease (CKD) and end-stage renal disease (ESRD). There is also growing evidence that AKI has long-term effects on overall survival; even many years after recovery from an episode AKI, patients suffer from premature death. We, the Translational Research Investigating Biomarkers in AKI Network (TRIBE-AKI Network), propose to conduct a landmark prospective cohort study of 1,800 patients (adult and pediatric) undergoing cardiac surgery at seven academic centers. We will study the entire cohort for the development of ESRD and death over time. Additionally, we will intensively follow 300 AKI patients and 300 randomly selected non-AKI patients for a mean of 4 years (range 3 to 5 years) in order to understand the long-term effects of AKI on the progression of kidney disease (change in glomerular filtration rate as determined by change in serum creatinine and change in serum cystatin C). The proposed study will be an extension of an NIH-funded study (R01-HL08676, funding from 04/07- 3/12) that is validating the role of newer biomarkers of AKI in the setting of cardiac surgery. The aims of this longitudinal study are: 1) to determine whether AKI is associated with accelerated decline in kidney function; 2) to determine the composite risk of ESRD and all-cause mortality in patients after AKI as defined by creatinine-based definitions of AKI; and 3) to evaluate the prognostic value of elevations in serum cystatin C and urinary biomarker concentrations (IL-18, NGAL) for the future development of ESRD and for mortality. The overall goals of this project are to determine the long-term associations between AKI and CKD and long-term mortality. We hypothesize that AKI will increase progression to CKD and contribute to premature death, and that the new biomarkers of AKI will be predictive of these outcomes. Public Health Relevance: The overall goals of this project are to determine the long-term associations between AKI and CKD and long-term mortality.